In this project, we will assess the impact of different sedative agents on the incidence of healthcare-associated infections and other complications of critical care in mechanically ventilated patients. This work has the potential to highlight a novel risk factor for healthcare-associated infection (HAI) and poor clinical outcomes, and may set the foundation for a prospective study of sedative management as a new strategy to reduce these infections. This study is critically important because 1) healthcare-associated infections continue to harm patients throughout American hospitals - especially intensive care patients - despite ample evidence and clear guidelines on how to prevent infections, and 2) there is sparse literature on the effect of sedative agents on infection risk, despite a rational clinical-biologicl basis for this relationship and suggestive data. Our first aim is to determine the relationship between different sedative agents and the relative rates of healthcare- associated infection in a mechanically ventilated patient population. We hypothesize that dexmedetomidine will carry a reduced risk of infection compared to propofol and benzodiazepines. We will perform a matched case-control study to evaluate this hypothesis. We will obtain clinical data from a comprehensive electronic health record search of 150 hospitals in the Hospital Corporation of America (HCA) network, as well as a manual chart review of HAI cases for data points not available electronically. Our analysis plan will be based on conditional logistic regression, including patients who are exposed to multiple agents simultaneously, with careful adjustment for potential confounders. Our second aim is to determine the effect of sedative choice and management on objective clinical outcomes in a mechanically ventilated population, including the duration of mechanical ventilation, the length of stay in the intensive care unit, and mortalit. It is known that non-benzodiazepine sedatives are optimal for reducing these outcomes compared to benzodiazepines, however it is not clear whether certain non-benzodiazepine agents of different mechanisms may have superior rates of these adverse events than others. We hypothesize that dexmedetomidine will reduce the morbidity and mortality of ventilated patients. We will perform a cohort study of patients based on sedative exposures, using an electronic query of HCA's clinical database for data collection. Analysis will include Cox proportional hazard regressions models with time-varying covariates to identify associations between exposures and outcomes.